Neuropsychologically relevant mental abilities are studied in healthy men at different ages, in patients with clinically- diagnosed Alzheimer's disease, and in adults with Down syndrome at different ages. Tests are administered to evaluate intelligence, memory, language, visual attention, visuoperceptive and visuoconstructive ability, and perceptual-motor speed. The presence and neuroanatomical location of separate visual pathways for spatial vision and object vision were demonstrated in healthy young men by measuring regional cerebral blood flow (rCBF) with positron emission tomography (PET) and H-2-15-0. Age-related differences on verbal processing and memory were not statistically significant in our sample of healthy men, ranging in age from 20 to 83 years, whereas, age-related differences on visuospatial processing and memory were significant but smaller than differences reported for non-health-screened adults. In healthy adults, visual memory and the discrepancy between verbal and visuospatial ability were not correlated with regional cerebral metabolic rates for glucose (rCMRglc) as measured by PET and 18-Fluorodeoxyglucose, but the discrepancy between visual and ; verbal memory was correlated with right-left parietal rCMRglc asymmetry. Neuropsychological patterns were correlated with neocortical rCMRglc patterns in patients with moderate Alzheimer's disease, but not in patients with mild Alzheimer's disease. Longitudinal study of mildly impaired patients, however, demonstrated that the development of neocortically-mediated neuropsychological impairments follows the appearance of significant neocortical rCMRglc abnormalities. Older Down syndrome adults without clinically significant dementia perform worse on memory and visuospatial construction tests than do younger subjects.